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Anti-epileptogenic effect of FC99 and resveratrol

Toll-like receptor 3 (TLR3), plays an important role in the development of epilepsy after brain insults. Previously, TLR3 deficiency in a pilocarpine model of temporal lobe epilepsy (TLE) was shown to reduce mortality, spontaneous recurrent seizures (SRS) and neuroinflammation. We hypothesized that...

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Autores principales: Shor, Oded, Rabinowitz, Roy, Hersh, Nir, Vanichkin, Alexey, Benninger, Felix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10483398/
https://www.ncbi.nlm.nih.gov/pubmed/37694107
http://dx.doi.org/10.3389/fnins.2023.1223196
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author Shor, Oded
Rabinowitz, Roy
Hersh, Nir
Vanichkin, Alexey
Benninger, Felix
author_facet Shor, Oded
Rabinowitz, Roy
Hersh, Nir
Vanichkin, Alexey
Benninger, Felix
author_sort Shor, Oded
collection PubMed
description Toll-like receptor 3 (TLR3), plays an important role in the development of epilepsy after brain insults. Previously, TLR3 deficiency in a pilocarpine model of temporal lobe epilepsy (TLE) was shown to reduce mortality, spontaneous recurrent seizures (SRS) and neuroinflammation. We hypothesized that pharmacological inhibition of TLR3 would reduce epileptogenesis following status epilepticus. We show that Resveratrol and FC99, two TLR3 blockers, demonstrate anti-epileptogenic effects in a pilocarpine model of TLE. While both Resveratrol and FC99 were previously shown to benefit in other pathologies, neither of these blockers had been proposed for the treatment of epilepsy. Our results provide substantial evidence to the importance of TLR3 inhibition in the prevention of epilepsy and specifically highlighting FC99 as a promising novel anti-epileptic drug. We anticipate our data to be a starting point for further studies assessing the anti-epileptogenic potential of FC99 and other TLR3 blockers, paving the way for pharmacological interventions that prevent epileptogenesis.
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spelling pubmed-104833982023-09-08 Anti-epileptogenic effect of FC99 and resveratrol Shor, Oded Rabinowitz, Roy Hersh, Nir Vanichkin, Alexey Benninger, Felix Front Neurosci Neuroscience Toll-like receptor 3 (TLR3), plays an important role in the development of epilepsy after brain insults. Previously, TLR3 deficiency in a pilocarpine model of temporal lobe epilepsy (TLE) was shown to reduce mortality, spontaneous recurrent seizures (SRS) and neuroinflammation. We hypothesized that pharmacological inhibition of TLR3 would reduce epileptogenesis following status epilepticus. We show that Resveratrol and FC99, two TLR3 blockers, demonstrate anti-epileptogenic effects in a pilocarpine model of TLE. While both Resveratrol and FC99 were previously shown to benefit in other pathologies, neither of these blockers had been proposed for the treatment of epilepsy. Our results provide substantial evidence to the importance of TLR3 inhibition in the prevention of epilepsy and specifically highlighting FC99 as a promising novel anti-epileptic drug. We anticipate our data to be a starting point for further studies assessing the anti-epileptogenic potential of FC99 and other TLR3 blockers, paving the way for pharmacological interventions that prevent epileptogenesis. Frontiers Media S.A. 2023-08-24 /pmc/articles/PMC10483398/ /pubmed/37694107 http://dx.doi.org/10.3389/fnins.2023.1223196 Text en Copyright © 2023 Shor, Rabinowitz, Hersh, Vanichkin and Benninger. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shor, Oded
Rabinowitz, Roy
Hersh, Nir
Vanichkin, Alexey
Benninger, Felix
Anti-epileptogenic effect of FC99 and resveratrol
title Anti-epileptogenic effect of FC99 and resveratrol
title_full Anti-epileptogenic effect of FC99 and resveratrol
title_fullStr Anti-epileptogenic effect of FC99 and resveratrol
title_full_unstemmed Anti-epileptogenic effect of FC99 and resveratrol
title_short Anti-epileptogenic effect of FC99 and resveratrol
title_sort anti-epileptogenic effect of fc99 and resveratrol
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10483398/
https://www.ncbi.nlm.nih.gov/pubmed/37694107
http://dx.doi.org/10.3389/fnins.2023.1223196
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